The purpose of this project is to enhance the quality of behavioral phenotyping and drug-screening techniques for zebrafish by analyzing the motivational effects of nicotine on zebrafish behavior. Although the study of zebrafish behavior is becoming popular (Gerlai 2003;Sison, Cawker et al. 2006), and their response to drugs such as nicotine seems to resemble that of humans and other mammals (Levin, Bencan et al. 2007;Eddins, Petro et al. 2009), it is not known whether these similarities extend below the surface, to common mechanisms. The purpose of this project is to explore the response of zebrafish to nicotine across a series of behavioral measures. One common behavioral measure of drug-induced reinforcement is Conditioned Place Preference (CPP), in which the preference for a drug-paired chamber is compared to a baseline preference (for reviews, see (Bardo and Bevins 2000;Tzschentke 2007)). The goal of this task is to measure the reinforcing properties of a drug, but interpretation of behavior in such a task is complicated by a variety of contextual factors. For example, it is often difficult to determine whether the drug has a rewarding effect, or whether it alleviates an aversive response to the testing chamber. Although nicotine-induced place preference has been observed in zebrafish (Kily, Cowe et al. 2008), the proposed anxiolytic effects of nicotine are confounded with rewarding effects in the experimental design that was used (Brielmaier, McDonald et al. 2008). The current project will explicitly compare behavior in a conditioned place preference task with that in an anxiety-related task to assess the relative effects of nicotine on anxiety-related and reward-related behaviors. Additionally, it will expand current knowledge of the behavioral effects of nicotine by measuring the same behaviors following chronic exposure and an abstinence interval. Zebrafish will be exposed either chronically or acutely to nicotine, and tested in a Black/White anxiety measure, a biased Black/White CPP test, or an unbiased Grey/Clear CPP test. The pattern of behavior across these three tasks will elucidate the relative roles of anxiety and reward systems underlying nicotine's behavioral effects. Ultimately, this will lead to a better understanding of the genetics and neural pathways involved in nicotine dependence in humans. PUBLIC HEALTH RELEVANCE: Because zebrafish are genetically and structurally similar to humans, their behavior may help us to better understand how drugs such as nicotine influence humans'brains and behavior. Initial research has indicated that nicotine may be rewarding for fish, as it is for humans. The goal of the current project is to look more closely at how nicotine affects reward and anxiety systems in zebrafish.